Sepsis, immunosuppression and the role of epigenetic mechanisms

ABSTRACT

Introduction: Sepsis has pro- and anti-inflammatory processes caused by infectious agents. Sepsis survivors have impaired immune response due to immunosuppression. Gene expression during the inflammatory process is guided by transcriptional access to chromatin, with post-translational changes made in histones that determine whether the loci of the inflammatory gene are active, balanced, or suppressed. For this, a review literature was performed in PubMed included ‘sepsis’ and ‘epigenetic’ and ‘immunosuppression’ terms until May 2020.

Areas covered: This review article explores the relationship between epigenetic mechanisms and the pathophysiology of sepsis. Epigenetic changes, vulnerable gene expression, and immunosuppression are related to inflammatory insults that can modify the dynamics of the central nervous system. Therefore, it is important to investigate the timing of these changes and their dynamics during the disease progression.

Expert opinion: Epigenetic changes are associated with the main stages of sepsis, from the pathogen-host interaction to inflammation and immunosuppression. These changes are key regulators of gene expression during physiological and pathological conditions. Thus, epigenetic markers have significant prognostic and diagnostic potential in sepsis, and epigenetic changes can be explored in combination with therapeutic strategies in experimental models of the disease.

KEYWORDS:

• Sepsis
• inflammation
• epigenetic
• gene expression
• immunosuppression

Article highlights

• Sepsis is a fatal organ dysfunction triggered by an unregulated immune response to an infectious agent.

• During the late stages of sepsis, anti-inflammatory cytokines are produced to decrease damage from the inflammatory response. This reaction acts on the host and can lead to immune tolerance.

• Sepsis-induced immunosuppression can be chronic, making patients susceptible to other complications.

• Epigenetics plays a key role in the regulation of inflammatory factors. In addition, epigenetic alterations are linked to the main stages of sepsis, including the pathogen-host interaction, immunosuppression, and inflammatory processes.

Declaration of interest

E da Silva Corneo, F Dal-Pizzol, M Michels are is supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by CAPES-001, FAPESC- 6/2017 and UNESC- PS826.